Integrated age‐related immunohistological changes occur in human olfactory epithelium and olfactory bulb

Abstract

Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity. However, this capability diminishes with advancing age and a decrease in odor perception in older individuals is well established. To characterize changes associated with age in the peripheral olfactory system, an in-depth analysis of the OE and its neuronal projections onto the olfactory bulb (OB) as a function of age was performed. Human olfactory tissue autopsy samples from 36 subjects with an average age of 74.1 years were analyzed.Established cell type-specific antibodies were used to identify OE component cells in whole mucosal sheets and epithelial sections as well as glomeruli and periglomerular structures in OB sections. With age, a reduction in OE area occurs across the mucosa progressing in a posterior-dorsal direction. Deterioration of the olfactory system is accompanied with diminution of neuron-containing OE, mature olfactory sensory neurons (OSNs) and OB innervation. On an individual level, the neuronal density within the epithelium appears to predict synapse density within the OB. The innervation of the OB is uneven with higher density at the ventral half that decreases with age as opposed to stable innervation at the dorsal half. Respiratory metaplasia, submucosal cysts, and neuromata, were commonly identified in aged OE. The finding of respiratory metaplasia and aneuronal epithelium with reduction in global basal cells suggests a progression of stem cell quiescence as an underlying pathophysiology of age-related smell loss in humans.

Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium

“…5G and fig. S7) ( 9 , 38 ). In both non–COVID-19 and post–COVID-19 normosmic groups, we identified prominent OMP + neurons and well-organized SOX2 + apical sustentacular cell nuclei.…”

“…To further validate the reduction in olfactory sensory neuron numbers identified by scRNA-seq, we performed immunohistochemical staining on additional samples, including non-COVID-19 normosmic (n = 3), post-COVID-19 normosmic (n = 2), and PASC hyposmic (n = 3) biopsies. We visualized mature olfactory sensory neurons with anti-olfactory marker protein (OMP) antibody (36)(37)(38) and sustentacular cells with apical layer anti-SOX2 antibody (Fig. 5G and fig.…”

Riechen und Riechstörungen

“…Traditionell wird angenommen, dass das Hauptriechepithel auf die Riechspalte im Dach der Nasenhöhle beschränkt ist. Es ist jedoch nicht ganz klar, welches Ausmaß das olfaktorische Epithel in der Nasenhöhle hat, da insbesondere bei jüngeren Menschen [34,35] reife und funktionelle olfaktorische sensorische Neurone am Ansatz der mittleren Nasenmuschel gefunden werden konnten [36][37][38][39][40]. Diese olfaktorischen Neurone besitzen apikal zur Oberfläche hin Zilien, die in den Schleim ragen und mit olfaktorischen Rezeptoren ausgekleidet sind [33].…”

Age-Related In Vivo Structural Changes in the Male Mouse Olfactory Bulb and Their Correlation with Olfactory-Driven Behavior

“…This implies that the OB maintains a rather juvenile environment with ageing. Nevertheless, the human OB volume has been shown to decline with age in autoptic material [ 9 ] and in vivo [ 1 ]. Investigation of the mouse brain cannot substitute that in the human; however, working on mice has the advantage of, e.g., limited inter-individual variability, because mouse social activities are simpler than those of humans, and a more homogeneous genetic background.…”